Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “PLACEBOS”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 397 records · Page 22Linked to original sources
PubMed1996

The uncontrollable placebo effect.

OBJECTIVE: To analyse the role of the control group in the methodology of clinical placebo effect evaluating trials. SETTING: Department of Medical Philosophy and Clinical Theory, University of Copenhagen. METHODS: A theoretical methodological analysis. RESULTS: At least with present trial designs, it is impossible, with certainty, to exclude a potential placebo effect from the so-called control group. The placebo effect, in other words, is uncontrollable. CONCLUSION: I suggest that the notions of control group and placebo treatment group are replaced by the notions of "placebo effect maximising group" and "placebo effect minimising group", thus stressing the fact that what such trials measure is a relative effect, and an underestimation of the absolute placebo effect. The illusion of absolute placebo effect evaluation must be acknowledged when articles referring to empirical trials on the placebo effect are interpreted.

Controlled Clinical Trials as Topic↗
PubMed2004

Placebo treatment is effective differently in different diseases--but is it also harmless? A brief synopsis.

UNLABELLED: The placebo drug reactions from controlled trials were studied for the first time systematically for efficacy and the safety in drug data pooled from randomized, placebo-controlled, multicentre studies. RESULTS: The efficacy of placebo on clinical symptoms and outcome varied between the therapeutic indications. However, no placebo effects on laboratory values, as e.g. blood glucose or Hb1c in diabetics, were noted. The frequency and type of placebo-induced adverse reactions also varied between indication groups. The placebo side effect profile was largely similar to the side effect profile of the active treatment. The mechanisms of placebo effects are many fold and varied (e.g. endorphin release, conditioning), much lacks explanation. CONCLUSION: Since the prescription of non-evidence based medicines (= pseudoplacebos) may clearly also result in serious adverse effects, such practice may not only be non-beneficial but may even be harmful. In clinical research, the judicious use of placebo remains essential to establish the efficacy and safety, safeguarding that patients receiving placebo will not be subject to harm and are fully informed.

Guidelines as Topic↗
PubMed1995

Lack of placebo effect on ambulatory blood pressure.

Several studies have reported that, at variance with clinic blood pressure, ambulatory blood pressure is not reduced by treatment with placebo. However, this evidence has usually been obtained in small groups of subjects and no data are available from a larger sample of patients. To address this issue we have analyzed data from 116 outpatients involved in placebo-controlled studies on antihypertensive treatment. The patients were studied before and at the end of a 6- to 8-week period of placebo. In all patients, blood pressure was measured by sphygmomanometry and over the 24 h by automatic ambulatory monitoring. Administration of placebo was accompanied by a significant reduction in systolic and diastolic clinic blood pressure (-5.3 +/- 1.1 and -4.4 +/- 0.6 mm Hg, respectively; P < .01), but not in 24-h, daytime and nighttime blood pressure. Hourly systolic and diastolic blood pressure profiles were virtually superimposable in the two different periods, except for the first 4 h, in which systolic blood pressure was slightly but significantly lower during than before placebo (149.5 +/- 1.2 v 146.4 +/- 1.2 mm Hg; P < .05). These results provide a large database indicating that 24-h average blood pressure is not reduced by placebo, thus it is not necessary to include a placebo control group in antihypertensive drug studies in which ambulatory blood pressure monitoring is employed. A small placebo effect occurs, however, in the first hours of ambulatory monitoring. This may lead to a slight overestimation of the peak blood pressure effect of a drug and an underestimation of its trough-to-peak ratio if placebo correction of the data is not made or if the first part of ambulatory blood pressure monitoring is not excluded from data analysis.

Blood Pressure↗
PubMed2005

Mechanisms of placebo analgesia: rACC recruitment of a subcortical antinociceptive network.

Placebo analgesia is one of the most striking examples of the cognitive modulation of pain perception and the underlying mechanisms are finally beginning to be understood. According to pharmacological studies, the endogenous opioid system is essential for placebo analgesia. Recent functional imaging data provides evidence that the rostral anterior cingulate cortex (rACC) represents a crucial cortical area for this type of endogenous pain control. We therefore hypothesized that placebo analgesia recruits other brain areas outside the rACC and that interactions of the rACC with these brain areas mediate opioid-dependent endogenous antinociception as part of a top-down mechanism. Nineteen healthy subjects received and rated painful laser stimuli to the dorsum of both hands, one of them treated with a fake analgesic cream (placebo). Painful stimulation was preceded by an auditory cue, indicating the side of the next laser stimulation. BOLD-responses to the painful laser-stimulation during the placebo and no-placebo condition were assessed using event-related fMRI. After having confirmed placebo related activity in the rACC, a connectivity analysis identified placebo dependent contributions of rACC activity with bilateral amygdalae and the periaqueductal gray (PAG). This finding supports the view that placebo analgesia depends on the enhanced functional connectivity of the rACC with subcortical brain structures that are crucial for conditioned learning and descending inhibition of nociception.

Adolescent↗
PubMed2001

Can placebo controls reduce the number of nonresponders in clinical trials? A power-analytic perspective.

BACKGROUND: There is ongoing debate regarding the ethics of placebo-controlled clinical trials when a moderately effective standard treatment exists. One aspect of the debate--the number of nonresponders--tends to be overlooked. A larger between-group effect size is expected in placebo-controlled trials than in trials with an active comparator. For that reason, substantially fewer subjects need to be enrolled in placebo-controlled trials; consequently, there tend to be far fewer nonresponders in placebo-controlled trials. OBJECTIVE: This analysis was undertaken to illustrate that the use of placebo as a control can reduce the number of subjects who are unnecessarily exposed to delayed treatment. METHODS: Statistical power analyses were used to estimate the sample size required to detect various population treatment differences and the resulting number of nonresponders for 2-tailed chi-square tests. RESULTS: Empiric evidence of the phenomenon is provided for a wide range of rates of response to placebo, investigational, and comparator treatments. For example, 24 subjects (ie, 12 per group) are needed to detect differences between placebo (10% response rate) and an investigational drug (70% response); 15 of these would not respond. In contrast, if the investigational drug (70% response) is initially compared with a standard therapy (60% response), 752 subjects would be required, 263 of whom would not respond. CONCLUSIONS: This paper shows empirically that placebo controls can reduce the number of nonresponders in a randomized controlled trial. The number of subjects who are exposed to unproven, albeit promising, investigational drugs should be kept to a minimum until placebo-controlled trials support their use.

Clinical Trials as Topic↗
PubMed2000

Efficacy and tolerability of a new 7-day transdermal estradiol patch versus placebo in hysterectomized women with postmenopausal complaints.

OBJECTIVES: To investigate the efficacy and tolerability of a continuously applied 7-day-Estradiol patch (Fem7, Merck KGaA, Germany) delivering 50 microg estradiol per day in the treatment of hysterectomized women with postmenopausal complaints compared with placebo. DESIGN: A multicentre, randomized, double-blind study with an initial screening phase (phase I), a 3-month double-blind placebo-controlled phase (phase II) and a 3-month open follow-up phase (phase III). METHODS: 186 patients were randomized for a 3-cycle placebo-controlled study followed by a 3-cycle open follow-up (total duration; 6 months). The changes in Kupperman Index (primary efficacy variable), hot flushes and urogenital symptom score were studied from baseline to the end of the study. In addition, skin tolerability was assessed and patients were also asked to grade the subjective acceptance of therapy. RESULTS: A reduction in Kupperman Index was observed in both groups, and at each cycle of the placebo-controlled treatment phase the 7-day-Estradiol patch was superior compared with placebo (last value vs. baseline P = 0.0006). From the second treatment week onwards a distinct difference was noted in the reduction of hot flushes from baseline between the 7-day-Estradiol patch group and the placebo group. The difference between the groups was statistically significant for each cycle and at the end of the controlled treatment phase (mean weekly hot flush reduction at the end of the placebo-controlled treatment phase: -32.5 for the 7-day-Estradiol patch vs. -22.0 for placebo, P = 0.0025). The efficacy of the 7-day-Estradiol patch within the application period did not show any difference between days 1-3 and 4-7. Subjective acceptance of the 7-day-Estradiol patch was good and 72.4% of patients who took active medication throughout the study were willing to consider continuing its use. CONCLUSIONS: The 7-day-Estradiol patch is well tolerated and provides effective relief of moderate to severe vasomotor symptoms in hysterectomized women, with a rapid onset of action and 7-day duration of therapeutic effect. Although a placebo effect was observed, the 7-day-Estradiol patch significantly reduced hot flushes and other menopausal symptoms throughout the application period.

Administration, Cutaneous↗
PubMed2003

A placebo for the pain: a medico-legal case analysis.

OBJECTIVES: The objectives of this medico-legal case report are to consider the current status of the use of placebos in pain medicine from clinical, ethical, and legal perspectives. The focus of the analysis is a particular case in which the deceptive use of placebo pain therapy on an adolescent gave rise to professional grievances filed by the patient's mother against the physician who ordered and several nurses who administered the placebo. The medical board declined to take disciplinary action against the physician, and disciplinary action by the board of registered nursing against the nurses was successfully challenged by two of the charged nurses in an administrative review. While there is a growing literature that challenges the need for or justification of the deceptive use of placebos, the practice continues and, as the case under consideration indicates, retains some influential supporters. DESIGN: This is a case report from a community hospital. The patient, referred to here as KC, was an adolescent with migraine headaches. The substitution of a placebo (saline solution) for an opioid analgesic (morphine) was made during KC's treatment. RESULTS: The patient's pain subsided sufficiently following the administration of a placebo to permit his discharge from the hospital. The subsequent discovery by the patient's mother of the deceptive use of a placebo prompted her to file charges of professional misconduct against the treating physician and three nurses with their respective professional licensing boards. The medical board declined to take disciplinary action against the physician, and the disciplinary action by the board of registered nursing was successfully challenged in a ruling by an administrative law judge following a hearing in which expert witnesses took conflicting positions on the acceptability of the deceptive use of a placebo. CONCLUSION: While there is a developing literature that challenges the ethical legitimacy of the deceptive use of placebos in pain medicine, that literature has yet to be recognized as unqualifiedly setting the standard of care or of professionalism in medicine and nursing.

Adolescent↗
PubMedDate not supplied

Efficacy and tolerability of tricyclic antidepressants and SSRIs compared with placebo for treatment of depression in primary care: a meta-analysis.

PURPOSE: Depression is common in primary care. There are no systematic reviews of depression treatment comparing antidepressants with placebo; hence, we do not know whether these medications are effective in primary care. METHODS: We searched the Cochrane Collaboration Depression, Anxiety and Neurosis Group register of controlled trials, MEDLINE, International Pharmaceutical abstracts, PsycINFO, and EMBASE. Abstracts of potential studies were reviewed independently by 2 authors. Studies needed to include randomized controlled trials of either a tricyclic antidepressant (TCA) or selective serotonin reuptake inhibitor (SSRI), or both, and placebo in a primary care setting. The data and quality of the studies were extracted and assessed by 2 authors blind to the other's choice. Disagreements were resolved by discussion. The main outcome measures were the standardized mean difference and weighted mean difference of the final mean depression scores, the relative risk of improvement, and the number withdrawing because of side effects. Pooling of results was done using Review Manager 4.2.2. RESULTS: There were 10 studies in which TCAs were compared with placebo, 3 in which SSRIs were compared with placebo, and 2 with both compared with placebo. One half of the studies were of low methodological quality, and nearly all studies were of short duration, typically 6 to 8 weeks. Pooled estimates of efficacy data showed a relative risk of 1.26 (95% CI, 1.12-1.42) for improvement with TCAs compared with placebo; For SSRIs, relative risk was 1.37 (95% CI, 1.21-1.55). Most patients, 56% to 60%, responded well to active treatment compared with 42% to 47% for placebo. The number needed to treat for TCAs was about 4, and for SSRIs it was 6. The numbers needed to harm (for withdrawal caused by side effects) ranged from 5 to 11 for TCAs and 21 to 94 for SSRIs. Low-dose (100 mg or 75 mg) as well as high-dose TCAs were effective. CONCLUSION: This systematic review is the first comparing antidepressants with placebo for treatment of depression in primary care. Both TCAs and SSRIs are effective. This review is also the first to show that low-dose TCAs are effective in primary care. Prescribing antidepressants in primary care is a more effective clinical activity than prescribing placebo.

Antidepressive Agents, Tricyclic↗
PubMed1994

A randomised clinical trial of the effect of informed consent on the analgesic activity of placebo and naproxen in cancer pain.

To determine whether informed consent in a therapeutic trial modifies the analgesic effect of naproxen and placebo, we conducted a prospective, randomised, single dose, placebo-controlled trial. Patients were randomly selected to receive or not information concerning the study. All patients included were then given a single dose of naproxen and placebo according to a crossover, double-blind design. Forty-nine patients with mild or moderate cancer pain which did not need narcotic analgesics entered the study. Twenty-five received both treatments without any information and constituted the uninformed group. Twenty-four had a complete information about the trial; six refused to participate. The 18 others constituted the informed-consent group. Visual analogue scales of pain before and 30, 60, 120 and 180 min after the intake of naproxen and placebo were recorded. As an analgesic, naproxen was more effective than placebo in both groups of patients (p = 0.001). For naproxen as well as for placebo, the analgesic effect was better in the informed-consent group compared to the uninformed group (p = 0.012). The difference in therapeutic activity between naproxen and placebo was moderately higher in the uninformed patients (p = 0.08). We concluded that, in contrast with parallel studies, giving information in a crossover, placebo-controlled trial may increase the apparent efficacy of both the tested agent and the placebo, and decrease the perceived difference the two.

Adult↗
PubMed2005

Past and present of ''what will please the lord'': an updated history of the concept of placebo.

In ecclesiastic tradition the term ''Placebo'' indicated the promise to please the Lord in medieval prayer. The expression ''Placebo Domino'' (''I shall please the Lord'') constituted the beginning of a famous passage of a V century A.D. translation of the Bible. It was in the second half of the XVIII century that the word Placebo became an integral part of the medical-pharmacological vocabulary, and in fact Quincy's Lexicon (1787) defined it as a remedy used more to please than to heal people. For centuries placebos have been considered precious deceptive therapies and, until 1945, they were generally considered to be morally useful management tools. At the end of World War II it was clear that a critical evaluation of the function of placebos was needed to shed some light on their real role. Following this methodological call, in the years following different studies on placebos were proposed, and in 1955 HK Beecher published in the JAMA a paper, ''The Powerful Placebo'', in which he concluded that it was evident that placebos had a high degree of therapeutic effectiveness. Recent evidence points to the fact that, on the contrary, placebos do not have major clinical effects and that the limits of their application should be fully acknowledged.

History, 18th Century↗
PubMed1994

The importance of placebo effects in pain treatment and research.

OBJECTIVE: To estimate the importance and implications of placebo effects in pain treatment and research from the existing literature, with emphasis on their magnitude and duration, the conditions influencing them, and proposed explanations. DATA SOURCES: English-language articles and books identified through MEDLINE (1980 through 1993) and PsycLIT (1967 through 1993) database searching, bibliography review, and expert consultation. STUDY SELECTION: Articles were included if they pertained to the review objectives. RESULTS: Placebo response rates vary greatly and are frequently much higher than the often-cited one third. Placebos have time-effect curves, and peak, cumulative, and carryover effects similar to those of active medications. As with medication, surgery can produce substantial placebo effects, and this possibility is commonly overlooked in case series reports on back surgery. Individuals are not consistent in their placebo responses, and a placebo-responder personality has not been identified. Models advanced to explain placebo effects emphasize the role of anxiety, expectations, and learning. CONCLUSIONS: Placebo effects influence patient outcomes after any treatment, including surgery, that the clinician and patient believe is effective. Placebo effects plus disease natural history and regression to the mean can result in high rates of good outcomes, which may be misattributed to specific treatment effects. The true causes of improvements in pain after treatment remain unknown in the absence of independently evaluated randomized controlled trials.

Dose-Response Relationship, Drug↗
PubMed2004

The course of chronic plaque-type psoriasis in placebo groups of randomized controlled studies.

OBJECTIVE: To determine the outcome in placebo-treated patients with plaque-type psoriasis. DATA SOURCES: Online search of MEDLINE and EMBASE until January 2001 and the Cochrane Library (2001, issue 1), supplemented by references, reviews, guidelines, and textbooks. STUDY SELECTION: Randomized controlled induction of remission trials of patients with chronic plaque-type psoriasis with systemic treatments with a placebo group not treated with antipsoriatic medication. Identified studies were examined by 2 independent reviewers. Through MEDLINE, 290 studies could be identified. Twenty-seven placebo-controlled studies were included (488 patients). DATA EXTRACTION: Two independent reviewers extracted data on first author, year of publication, design, comparison, placebo treatment, number of patients, treatment duration, type of psoriasis and baseline severity in the placebo group, mean relative change in outcome measures, and/or percentage of patients with worsening of psoriasis; no change; minimal, moderate, or good improvement; or complete clearance. DATA SYNTHESIS: Owing to substantial heterogeneity and differences in the way outcomes were reported, no summary estimates could be obtained. The outcome of placebo treatment was poor in most studies. Some reported a mean relative change of 11% to 47%. The highest percentages of patients ended up in the worsening, no change, or minimal improvement categories. Also, complete clearance was possible. No explanation for the differences in outcome between placebo groups could be found. Description of placebo groups was often insufficient. CONCLUSIONS: The effect of treatment in placebo groups varied across studies in an unpredictable way. To evaluate the variability, improvement of the standardization of study designs, entry criteria, and outcome measures is necessary in psoriasis trials.

Chronic Disease↗
PubMed1996

A placebo-controlled, randomized clinical trial comparing sertraline and imipramine for the treatment of dysthymia.

BACKGROUND: Despite the high prevalence of dysthymia and its associated morbidity, few controlled trials have evaluated the efficacy of antidepressant medication for this disorder. A 12-week, double-blind, placebo-controlled, randomized, multicenter trial was performed to evaluate the safety and efficacy of sertraline hydrochloride and imipramine hydrochloride in treating dysthymia. METHODS: A total of 416 outpatients (271 women and 145 men) aged 25 to 65 years with DSM-III-R-defined, early-onset, primary dysthymia without concurrent major depression were randomized to 12 weeks of treatment with sertraline, imipramine, or placebo. RESULTS: Both active treatments resulted in significantly reduced scores on the 17-item Hamilton Rating Scale for Depression (P = .04 and P = .01 for sertraline and imipramine vs placebo, respectively), the Montgomery-Asberg Depression Rating Scale (P = .01 and P = .003 vs placebo, respectively), Hopkins Symptom Checklist (P < .05), and the self-rated version of the Inventory of Depressive Symptoms (P < .05). With the use of a Clinical Global impressions improvement score of 1 or 2 (very much or much improved) to define response, response rates were 59% for sertraline, 64% for imipramine, and 44% for placebo (P = .02 for sertraline vs placebo and P < .001 for imipramine vs placebo). A significantly greater proportion of patients receiving imipramine than those receiving sertraline or placebo discontinued treatment because of adverse events (P = .001 and P < .001, respectively). CONCLUSIONS: Pharmacotherapy provides considerable relief from the symptoms of dysthymia in patients suffering from this chronic affective disorder, with both sertraline and imipramine being more effective than placebo. The greater tolerability of sertraline is an important consideration because of the chronicity of dysthymia, which may require prolonged treatment with antidepressant medication.

1-Naphthylamine↗
PubMed2001

Oral oestrogen replacement therapy versus placebo for hot flushes.

BACKGROUND: Hot flushes and night sweats are common symptoms experienced by menopausal women. Hormone replacement therapy (HRT), containing oestrogens alone or oestrogens together with progestogens in a cyclic or continuous regimen, is often recommended for their alleviation. OBJECTIVES: To examine the effect of oral HRT compared to placebo on these vasomotor symptoms and the risk of early onset side-effects. SEARCH STRATEGY: As developed by the Menstrual Disorders Group and Subfertility group of the Cochrane Collaboration. SELECTION CRITERIA: Double-blind, randomised, placebo-controlled trials of oral HRT therapy for at least three months duration. DATA COLLECTION AND ANALYSIS: Study quality and outcome data were assessed independently. Random effects models were considered appropriate due to the variety of trial methodologies. The meta-analyses were explored for sensitivity to trial quality and therapy duration. Symptom frequency and severity were assessed separately, together with withdrawals and side-effects. Frequency data were analysed using the Weighted Mean Difference (WMD) between treatment and placebo outcomes. For severity data, odds ratios were estimated from the proportional odds model. From 99 references originally identified, 21 trials meeting the selection criteria were included in the review. Study participants totalled 2,511. Trial duration ranged from three months to three years. MAIN RESULTS: There was a significant reduction in the weekly hot flush frequency for HRT compared to placebo (WMD -17.46, 95% CI -24.72, -10.21). This was equivalent to a 77% reduction in frequency (95% CI 58.2, 87.5) for HRT relative to placebo. Symptom severity was also significantly reduced compared to placebo (OR 0.13, 95% CI 0.08, 0.22). Withdrawal for lack of efficacy occurred significantly more often on placebo therapy (OR 17.25, 95% CI 8.23, 36.15). Withdrawal for adverse events, commonly breast tenderness, oedema, joint pain and psychological symptoms, was not significantly increased for HRT therapy (OR 1.38, 95% CI 0.87, 2.21). In women who were randomised to placebo treatment, a 50.8% (95% CI 41.7, 58.5) reduction in hot flushes was observed between baseline and end of study. REVIEWER'S CONCLUSIONS: Oral HRT is highly effective in alleviating hot flushes and night sweats. Therapies purported to reduce such symptoms must be assessed in blinded trials against a placebo or a validated therapy. Withdrawals due to side-effects were only marginally increased in the HRT groups despite the inability to tailor HRT in these fixed dose trials. Comparisons of hormonal doses, product types or regimens require analysis of trials with these specific "within study" comparisons.

Administration, Oral↗
PubMed2004

Pilot clinical trial of dehydroepiandrosterone (DHEA) versus placebo for Sjögren's syndrome.

OBJECTIVE: To screen for potential efficacy and assess feasibility and safety of dehydroepiandrosterone (DHEA) as a treatment for Sjögren's syndrome (SS). METHODS: A 24-week randomized, double-blinded, pilot trial of oral DHEA (200 mg/day) versus placebo was conducted. The primary comparison was to a hypothesized 20% placebo response rate. If 14 consecutive subjects on DHEA did not respond, a Phase III trial would be considered futile. A placebo group of 14 subjects was planned to verify placebo response rate and estimate sample size required for a definitive trial. Response criteria required 20% improvement in at least 2 of 3 domains. Analysis of covariance was used to adjust for baseline differences and for stratified randomization. Outcome measures included visual analog scale questionnaires for dry eye and dry mouth symptoms, lissamine green ocular dye staining and Schirmer I tests, stimulated salivary flow, IgG, and erythrocyte sedimentation rate (ESR). RESULTS: Randomization resulted in 14 DHEA and 14 placebo group subjects. At baseline, mean +/- SD for DHEA versus placebo groups were Schirmer I tests 4.5 +/- 4.5 versus 5.4 +/- 6.1 mm/5 minutes; Van Bijsterveld score 5.3 +/- 2.1 versus 5.5 +/- 2.2; unstimulated saliva 0.03 +/- 0.05 versus 0.04 +/- 0.10 ml/minute; IgG 1,699 +/- 749 versus 1,712 +/- 621 g/dl; and ESR 40 +/- 31 versus 44 +/- 28 mm/hour. Apart from changes over the trial in dry mouth symptoms, no significant differences were noted between the DHEA and placebo groups for dry eye symptoms, objective measures of ocular dryness, stimulated salivary flow; IgG, or ESR. Four DHEA and one placebo group patient dropped out because of adverse effects. Although 7 subjects met response criteria in the DHEA group, 5 met the criteria in the placebo group, and there was no significant difference between groups. CONCLUSION: DHEA showed no evidence of efficacy in SS. Without evidence for efficacy, patients with SS should avoid using unregulated DHEA supplements, since long-term adverse consequences of exposure to this hormone are unknown.

Adjuvants, Immunologic↗
PubMed1994

The expected drug and its expected effect interact to determine placebo responses to alcohol and caffeine.

This study tested placebo responses in psychomotor performance when caffeine or alcohol was expected. Fifty male university students were assigned to one of four placebo groups or to a no-treatment control group. Two groups received placebo caffeine and two received placebo alcohol. Subjects performed 12 trials on a pursuit rotor task and performance was measured by the percent time on target. Then they received information about the expected drug effect on the task. One caffeine placebo group (C+) and one alcohol placebo group (A+) were led to expect enhanced performance on the task. The other caffeine placebo group (C-) and alcohol placebo group (A-) were led to expect impaired performance. Subjects subsequently performed 12 trials on the task. An interaction was obtained between the expected type of effect and the expected type of drug. The C+ group displayed superior performance compared to the C- group, and the reverse relationship was observed between the A+ and A- group. In addition, subjects led to expect alcohol-induced impairment (A-) performed better than subjects led to expect caffeine-induced impairment (C-). Subjects also reported greater motivation to resist impairment when they expected alcohol rather than caffeine. The research indicates that understanding and predicting placebo responses may require consideration of the drug that is expected as well as its expected effect.

Adult↗
PubMed2002

Beta-blocker/thiazide combination for treatment of hypertensive children: a randomized double-blind, placebo-controlled trial.

Antihypertensive medications are used extensively in children despite a paucity of randomized, placebo-controlled trials. This study was among the first randomized, controlled pediatric antihypertensive medication trials, in which the combination drug bisoprolol fumarate/hydrochlorothiazide (B/HT) was compared with placebo. The study comprised a 2-week single-blind placebo screening period, a 6-week double-blind dose titration period, a 4-week double-blind dose maintenance period, and a 2-week double-blind dose-tapering period. One hundred and forty subjects were enrolled to achieve 94 randomized subjects treated either with B/HT ( n=62) or placebo ( n=32). B/HT induced significant reductions compared with placebo for average sitting systolic blood pressure (SiSBP) (9.3 vs. 4.9 mmHg, P<0.05) and sitting diastolic blood pressure (SiDBP) (7.2 vs. 2.7 mmHg, P<0.05). The placebo-subtracted BP reductions were greater in younger children and those with more-severe baseline hypertension. The percentage of subjects with BP less than the 90th percentile at study completion was 45% for B/HT and 34% for placebo ( P=NS). Although the study demonstrated that B/HT reduced BP safely compared with placebo, the large placebo effect and failure of most subjects to achieve target BP control make it uncertain whether B/HT is appropriate first-line therapy for pediatric hypertension, particularly in adolescents with mild-to-moderate BP elevation.

Adolescent↗
PubMed2003

Six-month efficacy of benfluorex vs. placebo or metformin in diet-failed type 2 diabetic patients.

Six-month efficacy of benfluorex (Mediator) (150-450 mg/day) was assessed in a double-blind multicenter study vs. placebo or metformin hydrochloride (850-2550 mg/day). After a 2-month run-in period of strict dieting, 722 type 2 diabetic patients were randomized (1:2:2) to receive placebo (n=144), benfluorex (n=294) or metformin (n=284). After a 5-week dose-finding phase, the efficacy of benfluorex was compared with that of placebo (test for difference, main analysis) and metformin (non-inferiority test, secondary analysis) during a 6-month fixed-dose treatment. At entry after strict dieting, there was no difference between groups for HbA(1C) (placebo, 7.4%+/-1.5%; benfluorex, 7.7%+/-1.6%; metformin, 7.8%+/-1.6%) and fasting plasma glucose (FPG; placebo, 9.7+/-2.3 mmol/l; benfluorex, 10.0+/-2.0 mmol/l; metformin, 10.2+/-2.5 mmol/l). At the end of the dose-finding phase, mean doses were 2.71 tablets/day for placebo group, 2.65 tablets/day for benfluorex (397.5 mg/day) and 2.50 tablets/day for metformin (2125 mg/day). At the end of treatment, HbA(1C) level decreased by 0.60% ( p<0.001) in benfluorex patients while it increased by 0.50% ( p<0.001) with placebo (intent-to-treat analysis). The mean endpoint difference was -0.86% (SE, 0.17%; p<0.001). Mean endpoint difference in HbA(1C) between benfluorex and metformin was 0.28% (SE, 0.12%) [90% CI, 0.07 to 0.48] (non-inferiority test, p=0.037). Treatment with benfluorex was well tolerated; 39% of these patients reported one or more emergent adverse events (compared to 38% on placebo and 43% on metformin) and only two patients suffered a treatment-related, serious adverse event. This study demonstrates that benfluorex: (1) significantly reduces HbA1C and fasting plasma glucose when compared to placebo; (2) has a good safety profile; and (3) has relatively lower potency compared to metformin, although the non-inferiority test (equivalence limit for HbA(1C) of 0.5%) was significant.

Appetite Depressants↗